Esfahanizadeh Marjan, Omidi Koroush, Kauffman Joel, Gudarzi Ali, Shahraki Zahedani Shahram, Amidi Salimeh, Kobarfard Farzad
Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. ; Central Research Laboratories, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Central Research Laboratories, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Pharm Res. 2014 Winter;13(1):115-26.
Treatment of tuberculosis (TB) and the discovery of effective new anti-tubercular drugs are among the most urgent priorities in health organizations all over the world. In the present study, fluorinated analogs of some of the most important anti-TB agents such as p-aminosalicylic acid (PAS), thiacetazone and pyrazinamide were synthesized and tested against TB. The fluorinated analog of thiacetazone was 20 times more potent than the parent compound against M.tuberculosis H37-RV, while the fluorinated p-aminosalicylic acid (PAS) was almost three times less potent than PAS. A few other halogenated analogs of thioacetazone were also synthesized and subjected to anti-M.tuberculosis screening tests. The best halogen substituent was found to be fluorine which has the smallest size from one hand and the strongest electronegativity from the other hand among the halogen atoms. Fluorine therefore could be considered as a golden substituent to improve the anti-M.tuberculosis activity of thioacetazone.
结核病（TB）的治疗以及有效新型抗结核药物的发现是全球卫生组织最紧迫的优先事项之一。在本研究中，合成了一些最重要的抗结核药物如对氨基水杨酸（PAS）、氨硫脲和吡嗪酰胺的氟化类似物，并对其进行了抗结核测试。氨硫脲的氟化类似物对结核分枝杆菌H37-RV的效力比母体化合物高20倍，而氟化对氨基水杨酸（PAS）的效力比PAS低近三倍。还合成了氨硫脲的其他一些卤化类似物，并进行了抗结核分枝杆菌筛选试验。发现最佳的卤素取代基是氟，因为在卤原子中，氟一方面尺寸最小，另一方面电负性最强。因此，氟可被视为提高氨硫脲抗结核活性的理想取代基。
